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BasictermsBacterialinfection(细菌的感染)Pathogen(病原菌)Nonpathogen(非病原菌)Opportunisticpathogen(机会致病菌)当前第1页\共有68页\编于星期四\16点BacterialInfection细菌的感染Theprocessofbacteriainvadinginthebody,growinginthetissues,producingtoxinsandcausingdiseasesiscalledbacterialinfection.当前第2页\共有68页\编于星期四\16点Pathogen(病原菌)Pathogenicbacterium(致病菌)Abacteriumwhichcancauseadiseaseiscalledpathogen.Nonpathogen(非病原菌)Nonpathogenicbacterium(非致病菌)Abacteriumthatdoesnotcausediseaseiscallednonpathogen.当前第3页\共有68页\编于星期四\16点Opportunisticpathogen(机会致病菌)Conditionedpathogen(条件致病菌)Somebacteriaarecapableofcausingdiseasesonlyundercertainconditions.Theseorganismscancausediseaseonlyifoneormoreoftheusualdefencemechanismshumanshaveevolvedtorestrictmicroorganismsfromtheirusuallysterileinternalorgansandtissuearebreachedbyaccident,byintent(e.g.surgery),orbyanunderlyingmetabolicoraninfectiousdisorder(e.g.AIDS).当前第4页\共有68页\编于星期四\16点OutlineNormalfloraandopportunisticpathogenBacterialpathogenesisThehostimmunedefencesystemTheinitiationandcourseofinfectionHospitalinfection当前第5页\共有68页\编于星期四\16点Section1

Normalfloraandopportunisticpathogen

正常菌群与机会致病菌当前第6页\共有68页\编于星期四\16点★Normalflora(正常菌群)Normalmicrobialflora(正常微生物群)Thepopulationofmicroorganismsthatinhabittheskinandmucousmembranesofhealthypersons.Theyareusuallyharmless,someevenbeneficial,tohuman’shealth.当前第7页\共有68页\编于星期四\16点LocationsSurfacetissuesofskinOralcavityRespiratorytractGastrointestinaltractGenitourinarytract当前第8页\共有68页\编于星期四\16点Normalfloraonintestinalmucosa当前第9页\共有68页\编于星期四\16点肠道的正常菌群当前第10页\共有68页\编于星期四\16点当前第11页\共有68页\编于星期四\16点★BeneficialeffectsofthenormalfloraBiologicalantagonism(生物拮抗)Productionofessentialnutrients(营养作用)Primingofimmunesystem(免疫作用)Anti-aging(抗衰老作用)当前第12页\共有68页\编于星期四\16点Biologicalantagonism(生物拮抗)Biologicalbarriers(生物屏障)orReceptorcompetition(受体竞争)Harmfulmetabolites(有害代谢产物)Nutrientcompetition(营养竞争)当前第13页\共有68页\编于星期四\16点Conditionedpathogen(条件致病菌)Somebacteriaarecapableofcausingdiseasesonlyundercertainconditions.Thesebacteriaarecalledopportunistic(conditioned)pathogensandthiskindofinfectioniscalledopportunisticinfection(机会性感染).★

Opportunisticpathogen(机会致病菌)当前第14页\共有68页\编于星期四\16点★

ConditionsofopportunisticinfectionChangeofinhabitingplaces(寄居部位改变)Immunesystemcompromise(宿主免疫功能低下)Dysbacteriosis(菌群失调)当前第15页\共有68页\编于星期四\16点Dysbacteriosis(菌群失调)Iffloradisequilibriumoccurs,forexample,whentheresidentfloraisdisturbed,somelittlesignificantmicroorganismsmaycolonize,proliferate,andproducedisease,whichiscalleddysbacteriosis.Dysbacteriosismainlyresultedfromlongtermandlargedosesantibioticstaken.当前第16页\共有68页\编于星期四\16点Superinfection(重叠感染)Afrequentcomplicationofdrugtherapyformicrobialinfection.Itmayresultfromopportunisticcolonizationfollowingimmunosuppressionbytheprimarypathogenandcanbeinfluencedbythetimeintervalbetweeninfections,microbialphysiology,orhostresistance.当前第17页\共有68页\编于星期四\16点Dysbacteriosisandsuperinfection当前第18页\共有68页\编于星期四\16点肠道的正常菌群健康青壮年粪便涂片健康老年粪便涂片(双歧杆菌)当前第19页\共有68页\编于星期四\16点Probiotics(益生菌)当前第20页\共有68页\编于星期四\16点Probiotics(益生菌)&Prebiotics(益生元)当前第21页\共有68页\编于星期四\16点Section2

BacterialPathogenesis

细菌的致病作用BasictermsBacterialPathogenicity

BacterialvirulenceNumberofinvadingorganismsPortalofentry当前第22页\共有68页\编于星期四\16点Pathogenicity(致病性)

isusedtodescribethecapacityofbacteriatoinitiatediseases.Thetermofvirulence(毒力)

isusedasacomparisonofpathogenicityinthequantitativesense.ID50(medianinfectiousdose,半数感染量):Infectiousdoseofbacteriafor50%ofthetestpopulation.LD50

(medianlethaldose,半数致死量)

:Lethaldoseofbacteriafor50%ofthetestpopulation.BasicTerms当前第23页\共有68页\编于星期四\16点ExotoxinPili(Fimbrial)CapsuleVirulentEnzymeAdhesinsFlagellaIronbindingproteinVirulencesurfaceproteinBacterialvirulencefactors(细菌毒力因子)当前第24页\共有68页\编于星期四\16点Bacterialvirulence(细菌的毒力)Virulence(毒力)Invasiveness(侵袭力)Toxin(毒素)Adherence&permanentplanting(黏附与定植)Multiplication&diffusion(增殖与扩散)Anti-defensefunctionofhost(免疫逃逸)Endotoxin(内毒素)Exotoxin(外毒素)当前第25页\共有68页\编于星期四\16点Adhesionandfieldplanting(黏附与定植)Invasion(侵入)Multiplicationanddiffusion(繁殖与扩散)Localdiffusion(局部扩散)Systemicdiffusion(全身性扩散)当前第26页\共有68页\编于星期四\16点★Invasiveness(侵袭力)Definition:Bacterialcapabilitythatcanbreakthroughthephysiologicbarriers(skin,mucosa),settledown,multiply,andspreadinthehost.Adhesivefactors:adhesinandcapsuleInvasivesubstancesBacterialbiofilm当前第27页\共有68页\编于星期四\16点1.Adhesin(黏附素)Protiensonbacterialsurfaceassociatedwithadhesion.Adhesinsbindtoadhesinreceptorsonhostcells.Classification:Pilus(fimbriae)adhesin(菌毛黏附素)Non-fimbriaeadhesin(非菌毛黏附素)当前第28页\共有68页\编于星期四\16点AdhesinAdhesinEpitheliumReceptorBacterium当前第29页\共有68页\编于星期四\16点Capsule(荚膜)ofstreptococcuspneumoniaeMicrocapsule(微荚膜)

Slimelayer(黏液层)当前第30页\共有68页\编于星期四\16点ProtectthecellwallagainstattackbydrugsInhibitingestionandkillingbyphagocytesPlayaroleintheadherenceofhumantissueAntigenicity2.Capsule(荚膜)当前第31页\共有68页\编于星期四\16点3.Invasiveenzymes侵袭性酶类Somebacteriamaygenerateinvasiveenzymes,whichcandamagebodytissuesandpromotetheinvasionanddiffusionofthebacteria.当前第32页\共有68页\编于星期四\16点4.Invasin侵袭素Encodedbyinvasivegenes(侵袭基因)Mediateinvadingadjacentepithelialcells当前第33页\共有68页\编于星期四\16点5.Bacterialbiofilm细菌生物被膜:Themembraneousbacterialcommunitycomposedofbacteriaandtheextracellularpolymerssecretedbybacteriaaftertheyadheretothesurfaceoflivingornonlivingmaterials.当前第34页\共有68页\编于星期四\16点5.Bacterialbiofilm细菌生物被膜FacilitatesbacterialadhesionBafflesthepenetrationofantibioticandtherejectionofimmunesystemProfitssignalcommunicationamongbacteria.当前第35页\共有68页\编于星期四\16点Bacterialbiofilm当前第36页\共有68页\编于星期四\16点当前第37页\共有68页\编于星期四\16点Biofilmintheendoscope(内窥镜)当前第38页\共有68页\编于星期四\16点Staphylococcusepidermidis(表皮葡萄球菌)biofilminthesurfaceofvenouscatheter(静脉导管)当前第39页\共有68页\编于星期四\16点ExotoxinsEndotoxinsExcretedbylivingcells;highconcentrationsinliquidmedium.IntegralpartofthecellwallofG-bacteria.Releasedonbacterialdeathandinpartduringgrowth.Maynotneedtobereleasedtohavebiologicactivity.ProducedbybothG+andG-bacteria.FoundonlyinG-bacteria.PolypeptidesLPS(lipidAportionprobablyresponsiblefortoxicity.)Relativelyunstable;toxicityoftendestroyedrapidlybyheatingattemperaturesabove60℃.Relativelystable;withstandheatingattemperaturesabove60℃forhourswithoutlossoftoxicity.当前第40页\共有68页\编于星期四\16点ExotoxinsEndotoxinsHighlyantigenic;stimulateformationofhigh-titerantitoxin(抗毒素).Antitoxinneutralizestoxin.Weaklyimmunogenic;antibodiesareantitoxicandprotective.Relationshipbetweenantibodytitersandprotectionfromdiseaseislessclearthanwithexotoxins.Convertedtoantigenic,nontoxictoxoids(类毒素)byformalin,acid,heat,etc.Toxoidsareusedtoimmunize.Notconvertedtotoxoids.Highlytoxic;fataltoanimalsinmicrogramquantitiesorless.Moderatelytoxic;fatalforanimalsintenstohundredsofmicrograms.当前第41页\共有68页\编于星期四\16点ExotoxinsEndotoxinsUsuallybindtospecificreceptorsoncells.Specificreceptorsnotfoundoncells.Usuallydonotproducefeverinthehost.Selectivetoxicityandspecificclinicalsyndromes.Neurotoxins(神经毒素)Cytotoxins(细胞毒素)Enterotoxins(肠毒素)UsuallyproducefeverinthehostbyreleaseofIL-1andothermediators.Frequentlycontrolledbyextrachromosomalgenes(e.g.plasmids).Synthesisdirectedbychromosomalgenes.当前第42页\共有68页\编于星期四\16点区别要点外毒素内毒素来源革兰阳性菌与部分革兰阴性菌革兰阴性菌编码基因质粒、前噬菌体或染色体基因染色体基因存在部分从活菌分泌出,少数菌崩解后释出细胞壁组分,菌裂解后释出化学成分蛋白质脂多糖稳定性60~80℃,30分钟破坏160℃,2~4小时破坏毒性作用强,对组织器官有选择性毒害效应,引起特殊的临床表现较弱,各菌的毒性效应大致相同,引起发热、白细胞增多、微循环障碍、休克、DIC等抗原性强,刺激机体产生抗毒素;甲醛液处理脱毒形成类毒素弱,刺激机体产生的中和抗体作用弱;甲醛液不能脱毒形成类毒素当前第43页\共有68页\编于星期四\16点SpecificpolysaccharideLPS当前第44页\共有68页\编于星期四\16点Procedure当前第45页\共有68页\编于星期四\16点Neurotoxin(神经毒素)Tetanustoxin(破伤风毒素)当前第46页\共有68页\编于星期四\16点Cytotoxins(细胞毒素)Diphtheriatoxin(白喉毒素)inhibitsproteinsynthesisinmammaliancellsandcausesnecrosisofcellsDiphtheriamembraneonthroat当前第47页\共有68页\编于星期四\16点Enterotoxin(肠毒素)Choleraenterotoxin当前第48页\共有68页\编于星期四\16点BiologicalrolesofendotoxinFever(发热)Leukopeniaandleukocytosis(白细胞反应)Endotoxemiaandshock(内毒素血症与休克)当前第49页\共有68页\编于星期四\16点EndotoxinActivatesmacrophagesActivatescomplementActivatesHagemanfactorIL-1,TNF,NitricoxideFeverandhypotensionC3a,C5aHypotensionEdemaCoagulationcascadeDIC当前第50页\共有68页\编于星期四\16点Section4

theinitiationandprocessofinfectionSourcesofinfectionPathwayofbacterialentranceTypesofbacterialinfection当前第51页\共有68页\编于星期四\16点Exogenousinfection(外源性感染)PatientsCarriers(带菌者)AnimalsEnodogenousinfection(内源性感染)OpportunisticpathogensSourcesofinfection当前第52页\共有68页\编于星期四\16点Pathwayofpathogenentrance

RespiratoryGastrointestinalGenitalSkinandmucosaAnimalbitesBloodSexualtransmission当前第53页\共有68页\编于星期四\16点TypesofbacterialinfectionInapparentinfection(隐性感染)Apparentinfection(显性感染)Carrierstate(带菌状态)当前第54页\共有68页\编于星期四\16点Inapparentinfection(隐性感染)Subclinicalinfection(亚临床型感染)Aninfectionthathasnoobservablesymptoms.Itoccurswhenthehostimmunityispotentorthepathogenicityofthepathogenisweak.当前第55页\共有68页\编于星期四\16点Thetipoftheiceberg

当前第56页\共有68页\编于星期四\16点Apparentinfection(显性感染)AcuteinfectionChronicinfectionLocalinfectionGeneralizedinfection★Toxemia(毒血症)Endotoxemia(内毒素血症)Bacteremia(菌血症)Septicemia(败血症)Pyemia(脓毒血症)当前第57页\共有68页\编于星期四\16点Toxemia(毒血症)Bacteriamutiplyatinvadinglocationanddonotenterbloodstream,buttheexotoxins(外毒素)enterbloodandcausecorrespondingtoxicsymptoms.Endotoxemia(内毒素血症)Gram-negativebacteriamutiplyatlocationorinbloodstream,releasealotofamountendotoxin(内毒素)releasedfrombacterialcellrupture.当前第58页\共有68页\编于星期四\16点Bacteremia(菌血症)Afterenteringblood,bacteriacirculatebutnotmultiplyintheblood.Septicemia(败血症)Bacteriacirculateandmultiplyintheblood,inwhichbacteriaproducetoxicproductsandcausehighswingingtypeoffeverandothertoxicsymptoms.当前第59页\共有68页\编于星期四\16点Pyemia(脓毒血症)Pyogenic(化脓性)bacteriaproducesepticemiawithmultipleabscesses(脓肿)ininternalorganssuchasspleen,liverandkidneys.当前第60页\共有68页\编于星期四\16点★

Carrierstate(带菌状态)Afterinapparentinfectionorapparentinfection,sometimesthepathogensarenoteliminatedintime,sothebacteriawillsurviveandmultiplyinhostatlowspeed,andbacteriaspreadintotheenvironment.Carrier(带菌者)isimportantsourceofinfection.当前第61页\共有68页\编于星期四\16点HospitalinfectionDefinitionBasiccharacteristicsClassificationMicrobialecologicalcharacteristicsEpidemiologicalc

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